The majority of eukaryotic genes contain introns, which are removed from the RNA polymerase II transcribed pre-messenger RNA by the splice some, to produce a mature mRNA. Defects in both pre-mRNA splicing and histone modifications have been implicated in human disease. Although transcription and RNA splicing have been studied as biochemical separate reactions, recent studies indicate that splicing occur co-transcription ally. Since co-transcriptional splicing occurs in the context of a chromatin, based upon our preliminary results, we are exploring how U2 snRNP proteins interact with the histone acetyltransferase, Gcn5 to coordinate transcription and pre-mRNA splicing. Using ChIP, we will examine how deletion of Gcn5 affects splicesome assembly. In addition, we will examine histone H3 acetylation and Gcn5 association to intronless and intron-containing genes when splicing factors are deleted. These finding will help us better understand the mechanism of the relationship between transcription and splicing as it relates to gene expression. Understanding these mechanisms will help us comprehend the origin of human disease and unveil possible new targets for the development of novel treatments for human disease.